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Öğe An In Vitro Study on the Cytotoxicity and Genotoxicity of Silver Sulfide Quantum Dots Coated with Meso-2,3-dimercaptosuccinic Acid(2019) Özkan Vardar, Deniz; Aydın, Sevtap; Hocaoğlu, İbrahim; Yağcı Acar, Havva Funda; Başaran, NurşenObjectives: Silver sulfide (Ag2 S) quantum dots (QDs) are highly promising nanomaterials in bioimaging systems due to their high activities for both imaging and drug/gene delivery. There is insufficient research on the toxicity of Ag2 S QDs coated with meso-2,3-dimercaptosuccinic acid (DMSA). In this study, we aimed to determine the cytotoxicity of Ag2 S QDs coated with DMSA in Chinese hamster lung fibroblast (V79) cells over a wide range of concentrations (5-2000 µg/mL). Materials and Methods: Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays. The genotoxic and apoptotic effects of DMSA/Ag2 S QDs were also assessed by comet assay and real-time polymerase chain reaction technique, respectively. Results: Cell viability was 54.0±4.8% and 65.7±4.1% at the highest dose (2000 µg/mL) of Ag2 S QDs using the MTT and NRU assays, respectively. Although cell viability decreased above 400 µg/mL (MTT assay) and 800 µg/mL (NRU assay), DNA damage was not induced by DMSA/Ag2 S QDs at the studied concentrations. The mRNA expression levels of p53, caspase-3, caspase-9, Bax, Bcl-2, and survivin genes were altered in the cells exposed to 500 and 1000 µg/mL DMSA/Ag2 S QDs. Conclusion: The cytotoxic effects of DMSA/Ag2 S QDs may occur at high doses through the apoptotic pathways. However, DMSA/Ag2 S QDs appear to be biocompatible at low doses, making them well suited for cell labeling applications.Öğe Development of novel self-assembled polymeric micelles from partially hydrolysed poly(2-ethyl-2-oxazoline)-co-PEI-b-PCL block copolymer as non-viral vectors for plasmid DNA in vitro transfection(Taylor and Francis Ltd., 2018) Kara, Aslı; Öztürk, Naile; Esendağlı, Güneş; Özköse, Umut Uğur; Gülyüz, Sevgi; Yılmaz, Özgür; Telci, Dilek; Bozkır, Asuman; Vural, İmranA new efficient, non-viral gene delivery cationic polymeric micellar system was developed by partial hydrolysis of poly(2-ethyl-2-oxazoline) (PEtOx) with two different hydrolysis percentages of PEtOx (30% and 60%) to reduce the disadvantages of the PEI. These self-assemble amphiphilic cationic micelles prepared from poly(2-ethyl-2-oxazoline) 30% -co-poly(ethyleneimine)-block-poly(?-caprolactone) (PEtOx 30% -co-PEI-b-PCL) (PPP30) and poly(2-ethyl-2-oxazoline) 60% -co-poly(ethyleneimine)-block-poly(?-caprolactone) (PEtOx 60% -co-PEI-b-PCL) (PPP60) block copolymers were successfully condensed with pEGFP-C3 plasmid DNA via electrostatic interactions to form micelle/DNA complexes with desirable particle sizes. All formulations showed low critical micelle concentration (CMC) values that means highly stable in serum containing medium. Polymeric micelles were also evaluated for their stability in the presence of serum and nuclease as well as cytotoxicity and transfection efficiency. All our results proved that our novel polymeric micellar system prepared by PPP60 block copolymer offer to be an efficient promising carrier for gene delivery applications. Moreover, these findings contribute to design and development of novel gene vectors with tunable and functionality features and also to reduce the cytotoxicity of PEI by partial hydrolysis of PEtOx an alternative synthesis method to produce linear PEI. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.Öğe Evaluation of the cytotoxic and genotoxic potential of lecithin/chitosan nanoparticles(2014) Taner, Gökçe; Yeşilöz, Recep; Özkan Vardar, Deniz; Şenyiğit, Taner; Özer, Özgen; Değen, Gisela H.; Başaran, NursenNanoparticles-based drug targeting delivery systems have been introduced in the treatment for various diseases because of their effective properties, although there have been conflicting results on the toxicity of nanoparticles. In the present study, the aim was to evaluate the cytotoxicity and the genotoxicity of different concentrations of lecithin/chitosan nanoparticles with and without clobetasol-17-propionate (CP) by neutral red uptake (NRU) cytotoxicity assay and single cell gel electrophoresis (Comet) and cytokinesis-blocked micronucleus assays. The IC50 values of lecithin/chitosan nanoparticles with/without CP were found as 1.9 and 1.8 %, respectively, in the NRU cytotoxicity test. High concentrations of lecithin/chitosan nanoparticles induced DNA damage in human lymphocytes as evaluated by comet assay. The micronucleus frequency was increased by the lecithin/chitosan treatment in a dose-dependent manner. Also at the two highest concentrations, a significant increase in micronucleus formation was observed. Lecithin/chitosan nanoparticles with CP did not increase the frequency of micronucleus and also did not induce additional DNA damage when compared with lecithin/chitosan nanoparticles without CP; therefore, CP itself has not found to be genotoxic at the studied concentration. © 2014 Springer Science+Business Media Dordrecht.Öğe Genetic variation in natural populations of Capparis from Turkey, as revealed by RAPD analysis(Springer-Verlag Wien, 2013) Özbek, Özlem; Kara, AslıIn this study, the genetic diversity of 15 Turkish natural Capparis populations was screened using the randomly amplified polymorphic DNA analysis (RAPD) technique. Ten RAPD primers produced 98 loci, 73 of which were polymorphic. The binary RAPD data were computed using the POPGENE (version 1.31), a genetic data analysis software program. According to genetic diversity analysis at locus level, the total genetic diversity (HT) and genetic diversity within population (Hs) were detected as 0.16 and 0.12, respectively. The genetic differentiation (GST) and gene flow (Nm) between populations were observed as 0.22 and 1.79, respectively. The mean number of allele per locus (na), the mean number of effective allele (nea), and the mean value of genetic diversity (He) were determined as 2, 1.20, and 0.16, respectively. According to Pearson’s correlation analysis, the mean number of allele had a strong negative correlation with wind and a strong positive correlation with rain. According to multiple regression analysis, eco-geographical factors had a significant effect on the mean number of allele, the mean number of effective allele, and the mean value of genetic diversity. The principal component analysis revealed 87.42% of total genetic variation. The principal coordinate analysis displayed the separation of population according to genetic distances based on dissimilarities matrix values on a scattered plot graph. Five different varieties, Capparis spinosa L. var. spinosa, var aegyptia and var. canescens, and Capparis ovata Desf. var. palaestina, and var. herbacea were identified in this study. Intermediate forms of plants were observed among the specimens. © Springer-Verlag Wien 2013.Öğe Lysozyme-loaded lipid-polymer hybrid nanoparticles: preparation, characterization and colloidal stability evaluation(Taylor and Francis Ltd., 2016) Devrim, Burcu; Kara, Aslı; Vural, İmran; Bozkır, AsumanContext: Lipid-polymer hybrid nanoparticles (LPNPs) are polymeric nanoparticles enveloped by lipid layers, which have emerged as a potent therapeutic nanocarrier alternative to liposomes and polymeric nanoparticles. Objective: The aim of this work was to develop, characterize and evaluate LPNPs to deliver a model protein, lysozyme. Materials and methods: Lysozyme-loaded LPNPs were prepared by using the modified w/o/w double-emulsion-solvent-evaporation method. Poly-?-caprolactone (PCL) was used as polymeric core material and tripalmitin:lechitin mixture was used to form a lipid shell around the LPNPs. LPNPs were evaluated for particle size distribution, zeta potential, morphology, encapsulation efficiency, in vitro drug release, stability and cytotoxicity. Results: The DLS measurement results showed that the particle size of LPNPs ranged from 58.04 ± 1.95 nm to 2009.00 ± 0.52 nm. The AFM and TEM images of LPNPs demonstrate that LPNPs are spherical in shape. The protein-loading capacity of LPNPs ranged from 5.81% to 60.32%, depending on the formulation parameters. LPNPs displayed a biphasic drug release pattern with a burst release within 1 h, followed by sustained release afterward. Colloidal stability results of LPNPs in different media showed that particle size and zeta potential values of particles did not change significantly in all media except of FBS 100% for 120 h. Finally, the results of a cellular uptake study showed that LPNPs were significantly taken up by 83.3% in L929 cells. Conclusion: We concluded that the LPNPs prepared with PCL as polymeric core material and tripalmitin:lechitin mixture as lipid shell should be a promising choice for protein delivery. © 2016 Informa UK Limited, trading as Taylor & Francis Group.Öğe Evaluation of antitumor activity of a non-steroidal anti-inflammatory drug, ibuprofen, by a targeted nanoparticulate system(Colegio de Farmaceuticos de la Provincia de Buenos Aires, 2017) Öztürk, Naile; Kara, Aslı; Vural, İmranIn this study we aimed to develop a new targeted nanoparticulate system to obtain site specific delivery of ibuprofen and to determine its antitumor efficiency. The potential effect of ibuprofen as an antitumor agent was investigated on breast cancer cells based on a targeted delivery system. Ibuprofen was encapsulated to poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA nanoparticles were fabricated by nanoprecipitation method and optimized in terms of certain parameters. Then, 520C9 monoclonal antibody (mAb) was chemically conjugated to carboxylic acid end group of PLGA nanoparticles (NPs) that specifically targeted human breast adenocarcinoma cell line (MCF-7). NP-mAb combined Ibuprofen encapsulated formulations were evaluated on characterization of particle size, encapsulation efficiency, drug loading capacity, and antitumor activity. The results demonstrated that optimized Ibuprofenloaded PLGA nanoparticles prepared by nanoprecipitation technique had an ideal particle size and polydispersity index. The encapsulation efficiency of optimized nanoparticles was relatively high, 92.9 ± 9.0%. Also, this system had significantly reduced the cell viability on MCF-7 cell line when compared with free ibuprofen solution at the same concentration. Above all, antibody-conjugated nanoparticles showed lower cell viability (12%) than the non-targeted system. Results indicated that ibuprofen-loaded nanoparticles had significant antitumor activity on MCF-7 cells even at relatively low concentrations. mAb conjugated drug-loaded nanoparticles were successfully fabricated and this system might be a promising approach for delivery of ibuprofen in treatment of breast cancer. © 2017, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.Öğe A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles(Elsevier B.V., 2017) Şekerdağ, Emine; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Öztürk, Naile; Kara, Aslı; Kaffashi, Abbas; Vural, İmran; Işıkay, İlkay; Yavuz, Burçin; Karlı Oğuz, Hatice Kader; Söylemezoğlu, Figen; Gürsoy Özdemir, Yasemin; Mut, MelikeNew drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brainbarrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10 days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500 mu M freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5 days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment.Öğe Use of in vitro assays to assess the potential cytotoxic, genotoxic and antigenotoxic effects of vanillic and cinnamic acid(Taylor and Francis Ltd, 2017) Taner, Gökçe; Özkan Vardar, Deniz; Aydın, Sevtap; Aytaç, Zeki; Başaran, Ahmet; Başaran, NurşenVanillic acid (VA) found in vanilla and cinnamic acid (CA) the precursor of flavonoids and found in cinnamon oil, are natural plant phenolic acids which are secondary aromatic plant products suggested to possess many physiological and pharmacological functions. In vitro and in vivo experiments have shown that phenolic acids exhibit powerful effects on biological responses by scavenging free radicals and eliciting antioxidant capacity. In the present study, we investigated the antioxidant capacity of VA and CA by the trolox equivalent antioxidant capacity (TEAC) assay, cytotoxicity by neutral red uptake (NRU) assay in Chinese Hamster Ovary (CHO) cells and also the genotoxic and antigenotoxic effects of these phenolic acids using the cytokinesis-blocked micronucleus (CBMN) and the alkaline comet assays in human peripheral blood lymphocytes. At all tested concentrations, VA (0.17–67.2 ?g/ml) showed antioxidant activity but CA (0.15–59.2 ?g/ml) did not show antioxidant activity against 2,2-azino-bis (3-ethylbenz-thiazoline-6-sulphonic acid) (ABTS). VA (0.84, 4.2, 8.4, 16.8, 84 and 168 ?g/ml) and CA (0.74, 3.7, 7.4, 14.8, 74, 148 ?g/ml) did not have cytotoxic and genotoxic effects alone at the studied concentrations as compared with the controls. Both VA and CA seem to decrease DNA damage induced by H2O2 in human lymphocytes. © 2016 Informa UK Limited, trading as Taylor & Francis Group.Öğe Effects of silver sulfide quantum dots coated with 2-mercaptopropionic acid on genotoxic and apoptotic pathways in vitro(Elsevier Ireland Ltd, 2018) Özkan Vardar, Deniz; Aydın, Sevtap; Hocaoğlu, İbrahim; Yağcı Acar, Funda Havva; Başaran, NursenQuantum dots (QDs) are highly promising nanomaterials in bioimaging system because of their bright fluorescence, broad UV excitation, narrow emission band, and high photostability. Recently, there is a great activity on Ag2S quantum dots for both imaging and drug/gene delivery due to the potential of having a better cytocompatability and near infrared luminescence. 2-Mercaptopropionic acid (2 MP A)-coated silver sulfide (Ag2S) QDs were reported as the most luminescent, stable, anionic Ag2S QDs in the literature. In this study, we aim to determine the cytotoxicity of 2 MP A/Ag2S in Chinese hamster lung fibroblast (V79) cells. The genotoxic and apoptotic effects of 2 MP A/Ag2S QDs were assessed by the alkaline single cell electrophoresis assay and real time polymerase chain reaction techniques, respectively. The cell viability decreased above 200 ?g/ml and 800 ?g/ml for MTT tetrazolium and neural red uptake assays, respectively. DNA damage was not observed by 2 MP A/Ag2S QDs at the studied concentration levels (5–2000 ?g/ml). The levels of mRNA expression of p53, caspase 3, caspase 9, bax, bcl-2, survivin were not changed by 2 MP A/Ag2S QDs below IC50 (around 1000 ?g/ml). Hence, 2 MP A/Ag2S QDs did not show any cytotoxic or genotoxic effects in V79 cells at lower doses. We conclude that the biocompatibility of 2 MP A/Ag2SODs makes them suitable for cell labeling applications. © 2018 Elsevier B.V.
